Related Experiment Video
Updated: Jul 16, 2026
08:27
Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology
Published on: March 24, 2015
Proteasome-independent HLA-B27 ligands arise mainly from small basic proteins
Miguel Marcilla1, Juan J Cragnolini, José A López de Castro
1Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain.
Molecular & Cellular Proteomics : MCP
|February 20, 2007
Summary
A significant portion of HLA-B27 peptide ligands are generated independently of the proteasome. These ligands primarily originate from small, basic proteins, suggesting a specialized non-proteasomal pathway in antigen presentation.
Area of Science:
- Immunology
- Molecular Biology
- Proteomics
Background:
- HLA-B27 is strongly associated with spondyloarthritis.
- Many constitutive peptide ligands of HLA-B27 are proteasome-independent.
Purpose of the Study:
- To determine the percentage and characteristics of proteasome-independent HLA-B27 ligands.
- To investigate the source proteins and proteolytic pathways involved in generating these ligands.
Main Methods:
- Stable isotope tagging and mass spectrometry were employed.
- Epoxomicin-mediated inhibition was used to assess proteasome dependence.
Main Results:
- 29.8% of examined HLA-B27 ligands were proteasome-independent.
- Proteasome-independent ligands were predominantly derived from small (6-16.5 kDa) and basic proteins.
- Proteasome-dependent and -independent ligands showed minimal differences in peptide motifs and flanking sequences.
Conclusions:
- A non-proteasomal proteolytic pathway with a preference for small proteins significantly contributes to the HLA-B27-bound peptide repertoire.
- This pathway plays a crucial role in antigen presentation by HLA-B27, particularly in the context of spondyloarthritis.
Related Concept Videos
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:31Antigen Processing Pathways
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...